Articles related to ACUTE MYELOID LEUKEMIA (AML)

Even after allogeneic hematopoietic stem-cell transplant (HCT), poor outcomes are typically the case in patients with TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The data from recent trials using the combination of eprenetapopt (APR-246) and azacitidine showed positive preclinical results in mTP53 AML/MDS, and this trial sought to assess the efficacy and safety of the eprenetapopt and azacitidine combination as maintenance therapy after allogeneic HCT in patients with mTP53 AML or MDS.

The study confirmed the high unmet need among older adults with AML, namely that overall survival (OS) without transplant is poor and consistent with other studies. The authors also remark that a “definitive evidence-based recommendation favoring venetoclax and azacitidine (ven/aza) or CPX-351 in older adults will require a randomized trial.”

The International Consensus Classification (ICC) of myeloid neoplasms and acute leukemia was developed as a result of the recent advances in doctors’ understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials.

In an integrated analysis of mutations and clinical outcomes, comprising 2,200 patients with TP53-mutated myelodysplastic syndrome (MDS) with excess blasts (EB) or TP53-mutated acute myeloid leukemia (AML), the authors state that mutant TP53 AML and MDS-EB “do not differ with respect to molecular characteristics and survival” and argue these entities should be considered a single molecular disease entity. In a commentary to the above paper, TP53 and the star-crossed lovers MDS and AML, John Welch, MD, PhD of Washington University School of Medicine writes, “As a junior Hematology/Oncology fellow, I was told there were two types of physicians: splitters and mergers. That is, clinicians either seek to diagnose increasingly homogenously narrow groups of patients based on increasingly refined, shared characteristics, or they seek to find broad, overarching patterns that unite diagnostic classifications. Hematologic malignancies have been fertile ground for the diagnostic splitters of the world. On the other hand, there have been some noteworthy exceptions. Sometimes it is a technological advance that allows for the synthesis of disparate diagnoses.”

Outcomes from the large PETHEMA registry study shows that secondary AML is common (27% of AML cases) and has a median OS of 5.6 months vs. 10.9 months for primary AML, and has various differing characteristics compared to primary AML. These include older age at diagnosis, more high-risk cytogenetics, less FMS-like tyrosine kinase three internal tandem duplication, fewer NPM1 mutations, and received a lower intensity of chemotherapy.

In this series from Blood that tackles four cases studies, the outcomes of AML pediatric patients compared to children with ALL is explored, focusing on the emerging new treatments venetoclax (Venclexta; AbbVie/Genentech), CD33- and CD123-directed CAR T-cell therapy, CD123-directed antibody therapy, and menin inhibitors.